PROJECT SUMMARY The overall goal of this project is to determine whether and how chronic psychosocial stressors might contribute to pre-clinical correlates of Alzheimer's disease (AD) and stroke in African-American women at midlife. It is well documented that older African-Americans have significantly higher rates of AD and stroke than their non-Hispanic white counterparts. However, in most studies of individuals over age 65, these disparities are already present, suggesting that factors responsible for the disparity occur much earlier in life. As the field has shifted to understanding the earliest changes in cognitive aging, the proposed project provides an unprecedented opportunity to investigate novel risk factors for adverse brain health in a recently funded study of vascular aging in African-American women aged 35-45. We will recruit a subsample of 100 African- American women of varying educational backgrounds from the parent study reporting high and low levels of chronic stress, respectively (N=50 from each group). Validated questionnaires will be utilized to measure overall chronic stress as well as chronic stressors known to be common among African-American women (i.e. discrimination, financial strain, neighborhood stressors and inadequate emotional support). Primary aims will compare high vs. low stress women on 1) measures of brain structure and vasculature (e.g. hippocampal volume and corticol thickness, microvascular disease, cerebral blood flow) using state of the art magnetic resonance imaging (MRI) techniques; as well as 2) cognitive function, using a brief neuropsychological battery. We will also examine whether established (nocturnal blood pressure, arterial stiffness) and novel (regenerative capacity) markers of overall vascular risk impact these outcomes among African-American women in the target age range. The overall objective of this R21 project is to obtain effect sizes for a larger, prospective, R01- funded study. The long-term goal of this program of research is to understand the impact of and pathways through which chronic stress contributes to risk for AD and stroke in an understudied, yet vulnerable group of women.